Human Gene BCL2L11 (uc002tgv.1)
  Description: Homo sapiens BCL2-like 11 (apoptosis facilitator) (BCL2L11), transcript variant 1, mRNA.
RefSeq Summary (NM_138621): The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The protein encoded by this gene contains a Bcl-2 homology domain 3 (BH3). It has been shown to interact with other members of the BCL-2 protein family and to act as an apoptotic activator. The expression of this gene can be induced by nerve growth factor (NGF), as well as by the forkhead transcription factor FKHR-L1, which suggests a role of this gene in neuronal and lymphocyte apoptosis. Transgenic studies of the mouse counterpart suggested that this gene functions as an essential initiator of apoptosis in thymocyte-negative selection. Several alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2013].
Transcript (Including UTRs)
   Position: hg19 chr2:111,878,491-111,926,022 Size: 47,532 Total Exon Count: 4 Strand: +
Coding Region
   Position: hg19 chr2:111,881,323-111,921,808 Size: 40,486 Coding Exon Count: 3 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:111,878,491-111,926,022)mRNA (may differ from genome)Protein (198 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
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OMIMPubMedReactomeTreefamUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: B2L11_HUMAN
DESCRIPTION: RecName: Full=Bcl-2-like protein 11; Short=Bcl2-L-11; AltName: Full=Bcl2-interacting mediator of cell death;
FUNCTION: Induces apoptosis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.
SUBUNIT: Forms heterodimers with a number of antiapoptotic Bcl-2 proteins including MCL1, BCL2, BCL2L1 isoform Bcl-X(L), BCL2A1/BFL-1, BHRF1, and BCLW. Isoform BimS and isoform Bim-alpha3 interact with BAX; this interaction induces the conformationally active form of BAX. Does not heterodimerize with proapoptotic proteins such as BAD, BOK or BAK (By similarity). Interacts with DYNLL1 and YWHAZ (By similarity). When phosphorylated, interacts with TRIM2; this interaction is associated with ubiquitination and degradation (By similarity).
INTERACTION: Q07812:BAX; NbExp=11; IntAct=EBI-526406, EBI-516580; P10415:BCL2; NbExp=4; IntAct=EBI-526420, EBI-77694; Q07440:Bcl2a1 (xeno); NbExp=2; IntAct=EBI-526406, EBI-707754; Q07817-1:BCL2L1; NbExp=8; IntAct=EBI-526406, EBI-287195; Q92843:BCL2L2; NbExp=4; IntAct=EBI-526406, EBI-707714; P63244:GNB2L1; NbExp=2; IntAct=EBI-526406, EBI-296739; Q07820:MCL1; NbExp=6; IntAct=EBI-526406, EBI-1003422; P97287:Mcl1 (xeno); NbExp=5; IntAct=EBI-526406, EBI-707292; P14174:MIF; NbExp=5; IntAct=EBI-526420, EBI-372712;
SUBCELLULAR LOCATION: Endomembrane system; Peripheral membrane protein (By similarity). Note=Associated with intracytoplasmic membranes (By similarity).
SUBCELLULAR LOCATION: Isoform BimEL: Mitochondrion.
SUBCELLULAR LOCATION: Isoform BimL: Mitochondrion.
SUBCELLULAR LOCATION: Isoform BimS: Mitochondrion.
SUBCELLULAR LOCATION: Isoform Bim-alpha1: Mitochondrion.
TISSUE SPECIFICITY: Isoform BimEL, isoform BimL and isoform BimS are the predominant isoforms and are ubiquitously expressed with a tissue-specific variation. Isoform Bim-gamma is most abundantly expressed in small intestine and colon, and in lower levels in spleen, prostate, testis, heart, liver and kidney.
INDUCTION: By ER stress in a DDIT3/CHOP-dependent manner.
DOMAIN: The BH3 motif is required for Bcl-2 binding and cytotoxicity.
PTM: Phosphorylation by MAPK1/MAPK3 induces interaction with TRIM2, followed by ubiquitination (By similarity).
PTM: Ubiquitinated by TRIM2 following phosphorylation by MAPK1/MAPK3, leading to degradation by the proteasome (By similarity).
SIMILARITY: Belongs to the Bcl-2 family.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/BCL2L11ID772ch2q13.html";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): BCL2L11
CDC HuGE Published Literature: BCL2L11
Positive Disease Associations: Cholangitis, Sclerosing , Chronic lymphocytic leukemia , Coronary Disease , Dehydroepiandrosterone Sulfate
Related Studies:
  1. Cholangitis, Sclerosing
    Espen Melum et al. Nature genetics 2011, Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci., Nature genetics. [PubMed 21151127]
  2. Chronic lymphocytic leukemia
    Di Bernardo ,et al. 2008, A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia, Nature genetics 2008 40- 10 : 1204-10. [PubMed 18758461]
  3. Coronary Disease
    , , . [PubMed 0]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: BCL2L11
Diseases sorted by gene-association score: ocular hyperemia (8), autoimmune lymphoproliferative syndrome (5), colorectal cancer (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 10.05 RPKM in Thyroid
Total median expression: 174.79 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -94.30288-0.327 Picture PostScript Text
3' UTR -1309.384214-0.311 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR014771 - Apoptosis_Bim_N
IPR017288 - Bcl-2-like_11
IPR015040 - Bcl-x_interacting

Pfam Domains:
PF06773 - Bim protein N-terminus
PF08945 - Bcl-x interacting, BH3 domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2K7W - NMR MuPIT 2NL9 - X-ray MuPIT 2V6Q - X-ray 2VM6 - X-ray MuPIT 2WH6 - X-ray 3D7V - X-ray MuPIT 3FDL - X-ray MuPIT 3IO8 - X-ray MuPIT 3IO9 - X-ray MuPIT 3KJ0 - X-ray MuPIT 3KJ1 - X-ray MuPIT 3KJ2 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on O43521
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0008017 microtubule binding
GO:0019901 protein kinase binding
GO:0046982 protein heterodimerization activity
GO:0070840 dynein complex binding

Biological Process:
GO:0001701 in utero embryonic development
GO:0001776 leukocyte homeostasis
GO:0001782 B cell homeostasis
GO:0001783 B cell apoptotic process
GO:0001822 kidney development
GO:0001844 protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
GO:0002260 lymphocyte homeostasis
GO:0002262 myeloid cell homeostasis
GO:0006915 apoptotic process
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0007160 cell-matrix adhesion
GO:0007283 spermatogenesis
GO:0007420 brain development
GO:0008584 male gonad development
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
GO:0009791 post-embryonic development
GO:0010942 positive regulation of cell death
GO:0030879 mammary gland development
GO:0032464 positive regulation of protein homooligomerization
GO:0034976 response to endoplasmic reticulum stress
GO:0035148 tube formation
GO:0042475 odontogenesis of dentin-containing tooth
GO:0042981 regulation of apoptotic process
GO:0043029 T cell homeostasis
GO:0043065 positive regulation of apoptotic process
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043525 positive regulation of neuron apoptotic process
GO:0043583 ear development
GO:0045787 positive regulation of cell cycle
GO:0046620 regulation of organ growth
GO:0048066 developmental pigmentation
GO:0048070 regulation of developmental pigmentation
GO:0048536 spleen development
GO:0048538 thymus development
GO:0048563 post-embryonic animal organ morphogenesis
GO:0060139 positive regulation of apoptotic process by virus
GO:0060154 cellular process regulating host cell cycle in response to virus
GO:0070242 thymocyte apoptotic process
GO:0071385 cellular response to glucocorticoid stimulus
GO:0090200 positive regulation of release of cytochrome c from mitochondria
GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
GO:1902110 positive regulation of mitochondrial membrane permeability involved in apoptotic process
GO:1902237 positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
GO:1902263 apoptotic process involved in embryonic digit morphogenesis
GO:1903896 positive regulation of IRE1-mediated unfolded protein response
GO:2000271 positive regulation of fibroblast apoptotic process
GO:2001244 positive regulation of intrinsic apoptotic signaling pathway
GO:0007127 meiosis I

Cellular Component:
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005741 mitochondrial outer membrane
GO:0005829 cytosol
GO:0005868 cytoplasmic dynein complex
GO:0012505 endomembrane system
GO:0016020 membrane
GO:0019898 extrinsic component of membrane
GO:0043231 intracellular membrane-bounded organelle
GO:0097136 Bcl-2 family protein complex
GO:0097140 BIM-BCL-xl complex
GO:0097141 BIM-BCL-2 complex
GO:0005874 microtubule


-  Descriptions from all associated GenBank mRNAs
  LF205885 - JP 2014500723-A/13388: Polycomb-Associated Non-Coding RNAs.
LF213705 - JP 2014500723-A/21208: Polycomb-Associated Non-Coding RNAs.
AK291269 - Homo sapiens cDNA FLJ75935 complete cds, highly similar to Homo sapiens BCL2-like 11 (apoptosis facilitator) (BCL2L11), transcript variant 1, mRNA.
AK290377 - Homo sapiens cDNA FLJ75915 complete cds, highly similar to Homo sapiens BCL2-like 11 (apoptosis facilitator) (BCL2L11), transcript variant 6, mRNA.
BC033694 - Homo sapiens BCL2-like 11 (apoptosis facilitator), mRNA (cDNA clone MGC:45206 IMAGE:5213713), complete cds.
AY352518 - Homo sapiens Bcl2-interacting mediator gamma (BIM) mRNA, complete cds; alternatively spliced.
AB463437 - Synthetic construct DNA, clone: pF1KB4054, Homo sapiens BCL2L11 gene for BCL2-like 11, without stop codon, in Flexi system.
CU689702 - Synthetic construct Homo sapiens gateway clone IMAGE:100022741 5' read BCL2L11 mRNA.
HQ447452 - Synthetic construct Homo sapiens clone IMAGE:100070781; CCSB015065_01 BCL2-like 11 (apoptosis facilitator) (BCL2L11) gene, encodes complete protein.
KJ892898 - Synthetic construct Homo sapiens clone ccsbBroadEn_02292 BCL2L11 gene, encodes complete protein.
AB071195 - Homo sapiens mRNA for Bim-alpha1, complete cds.
AB071196 - Homo sapiens mRNA for Bim-alpha2, complete cds.
AB071197 - Homo sapiens mRNA for Bim-beta1, complete cds.
AB071198 - Homo sapiens mRNA for Bim-beta2, complete cds.
AB071199 - Homo sapiens mRNA for Bim-beta3, complete cds.
AB071200 - Homo sapiens mRNA for Bim-beta4, complete cds.
AF032457 - Homo sapiens BimEL mRNA, complete cds.
AF032458 - Homo sapiens BimL mRNA, complete cds.
AY305714 - Homo sapiens BCL2-like 11 transcript variant 9 mRNA, complete cds; alternatively spliced.
AY305715 - Homo sapiens BCL2-like 11 transcript variant 10 mRNA, complete cds; alternatively spliced.
AY305716 - Homo sapiens bim beta 5 mRNA, complete cds, alternatively spliced.
AY423441 - Homo sapiens BIM-alpha3 (BCL2L11) mRNA, complete cds, alternatively spliced.
AY423442 - Homo sapiens BIM-alpha4 (BCL2L11) mRNA, complete cds, alternatively spliced.
AY423443 - Homo sapiens BIM-alpha5 (BCL2L11) mRNA, complete cds, alternatively spliced.
AY428962 - Homo sapiens BIM-BETA5 mRNA, complete cds; alternatively spliced.
DQ849200 - Homo sapiens BIM-alpha6 mRNA, complete cds, alternatively spliced.
DQ849201 - Homo sapiens BIM-beta6 mRNA, complete cds, alternatively spliced.
DQ849202 - Homo sapiens BIM-beta7 mRNA, complete cds, alternatively spliced.
JA397949 - Sequence 14 from Patent EP2331135.
JA397950 - Sequence 15 from Patent EP2331135.
JA397951 - Sequence 16 from Patent EP2331135.
AF455755 - Homo sapiens BAM mRNA, complete cds.
AF086141 - Homo sapiens full length insert cDNA clone ZA94C02.
AK027160 - Homo sapiens cDNA: FLJ23507 fis, clone LNG03128.
JD249454 - Sequence 230478 from Patent EP1572962.
JD247957 - Sequence 228981 from Patent EP1572962.
JD499553 - Sequence 480577 from Patent EP1572962.
JD272659 - Sequence 253683 from Patent EP1572962.
JD489829 - Sequence 470853 from Patent EP1572962.
JD515517 - Sequence 496541 from Patent EP1572962.
JD317268 - Sequence 298292 from Patent EP1572962.
JD180550 - Sequence 161574 from Patent EP1572962.
JD477508 - Sequence 458532 from Patent EP1572962.
JD250972 - Sequence 231996 from Patent EP1572962.
JD111440 - Sequence 92464 from Patent EP1572962.
JD111441 - Sequence 92465 from Patent EP1572962.
JD220356 - Sequence 201380 from Patent EP1572962.
JD154468 - Sequence 135492 from Patent EP1572962.
JD162447 - Sequence 143471 from Patent EP1572962.
JD496414 - Sequence 477438 from Patent EP1572962.
JD368797 - Sequence 349821 from Patent EP1572962.
JD374498 - Sequence 355522 from Patent EP1572962.
JD306131 - Sequence 287155 from Patent EP1572962.
JD244338 - Sequence 225362 from Patent EP1572962.
JD284125 - Sequence 265149 from Patent EP1572962.
JD061435 - Sequence 42459 from Patent EP1572962.
JD503365 - Sequence 484389 from Patent EP1572962.
JD039554 - Sequence 20578 from Patent EP1572962.
JD097950 - Sequence 78974 from Patent EP1572962.
JD180935 - Sequence 161959 from Patent EP1572962.
JD565761 - Sequence 546785 from Patent EP1572962.
JD350727 - Sequence 331751 from Patent EP1572962.
JD025224 - Sequence 6248 from Patent EP1572962.
JD031994 - Sequence 13018 from Patent EP1572962.
MA441462 - JP 2018138019-A/13388: Polycomb-Associated Non-Coding RNAs.
MA449282 - JP 2018138019-A/21208: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein O43521 (Reactome details) participates in the following event(s):

R-HSA-139919 Translocation of BIM to mitochondria
R-HSA-139918 Phosphorylation of BIM by JNK
R-HSA-205075 JNK phosphorylates BIM, BAD and other targets
R-HSA-508163 BH3-only proteins associate with and inactivate anti-apoptotic BCL-2
R-HSA-508162 BH3 only proteins associate with and inactivate anti-apoptotic BCL-XL
R-HSA-6802927 BRAF and RAF fusion mutant dimers are phosphorylated
R-HSA-6802934 p-BRAF and RAF fusion dimers bind MAP2Ks and MAPKs
R-HSA-6802932 Dissociation of BRAF/RAF fusion complex
R-HSA-6802933 p-BRAF and RAF fusion dimers phosphorylate MAP2Ks
R-HSA-6802935 MAPKs are phosphorylated downstream of BRAF and RAF fusion dimers
R-HSA-111446 Activation of BIM and translocation to mitochondria
R-HSA-193648 NRAGE signals death through JNK
R-HSA-8952158 RUNX3 regulates BCL2L11 (BIM) transcription
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models
R-HSA-114452 Activation of BH3-only proteins
R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE
R-HSA-8878159 Transcriptional regulation by RUNX3
R-HSA-8863678 Neurodegenerative Diseases
R-HSA-111453 BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members
R-HSA-109606 Intrinsic Pathway for Apoptosis
R-HSA-193704 p75 NTR receptor-mediated signalling
R-HSA-212436 Generic Transcription Pathway
R-HSA-1643685 Disease
R-HSA-6802952 Signaling by BRAF and RAF fusions
R-HSA-109581 Apoptosis
R-HSA-73887 Death Receptor Signalling
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-6802957 Oncogenic MAPK signaling
R-HSA-5357801 Programmed Cell Death
R-HSA-162582 Signal Transduction
R-HSA-74160 Gene expression (Transcription)
R-HSA-5663202 Diseases of signal transduction

-  Other Names for This Gene
  Alternate Gene Symbols: A8K2W2, B2L11_HUMAN, BIM, NM_138621, NP_619527, O43521, O43522, Q0MSE7, Q0MSE8, Q0MSE9, Q53R28, Q6JTU6, Q6T851, Q6TE14, Q6TE15, Q6TE16, Q6V402, Q8WYL6, Q8WYL7, Q8WYL8, Q8WYL9, Q8WYM0, Q8WYM1
UCSC ID: uc002tgv.1
RefSeq Accession: NM_138621
Protein: O43521 (aka B2L11_HUMAN)
CCDS: CCDS2089.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_138621.4
exon count: 4CDS single in 3' UTR: no RNA size: 5106
ORF size: 597CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1369.50frame shift in genome: no % Coverage: 99.86
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: yes # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
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-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.